PEGylation of PLA nanoparticles to improve mucus-penetration and colloidal stability for oral delivery systems Juliana Palacio, Natalia A Agudelo and Betty Lucy Lopez Poly(lactic acid) (PLA) nanoparticles are one of the most studied systems for drug delivery due to their biodegradability and biocompatibility. However, oral administration, which is a non-invasive and convenient route, is limited by PLA hydrophobicity as well as low chemical and colloidal stability in the gastrointestinal track. These drawbacks can be overcome by coating the PLA nanoparticle surface with hydrophilic polymers, such as polyethylene glycol, and controlling the coverage density. This type of modification is being extensively explored for oral drug delivery. The challenges associated with the delivery of these nanoparticles depend greatly on the surface properties, such as hydrophobicity, charge and particle size. This review highlights nanoparticle design considerations for overcoming physiological hurdles (i.e. chemical and enzymatic barriers) for the oral administration of drugs. Address Grupo de Investigacio ´n Ciencia de los Materiales, Instituto de Quı´mica, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Calle 70 N8 52-21, Medellı´n, Colombia Corresponding author: Palacio, Juliana (juli.pb@gmail.com) Current Opinion in Chemical Engineering 2016, 11:14–19 This review comes from a themed issue on Materials engineering Edited by Thein Kyu and Jai A Sekhar http://dx.doi.org/10.1016/j.coche.2015.11.006 2211-3398/# 2015 Elsevier Ltd. All rights reserved. Introduction Oral administration is the most preferred route for the administration of drugs because it offers the greatest degree of patient compliance and is a very effective route for drugs that exhibit high water solubility and gastroin- testinal (GI) permeability. However, the oral administra- tion of drugs with poor water solubility and/or permeability and/or metabolic stability is very challeng- ing, which affects the delivery of many existing drugs. The GI tract presents various chemical (pH variations) and enzymatic barriers that affect the oral administration of drugs, resulting in their degradation, low absorption and low bioavailability. In general, these drugs have to be administered at high doses to achieve therapeutic concentration [1  ,2  ,3–5]. Developments in nanomedi- cine are expected to provide solutions to many of the unsolved problems in modern medicine. For oral admin- istration, nanotechnology has revolutionized the field of drug delivery research [6]. In recent years, the focus has been on the fabrication of polymeric nanoparticles as oral drug delivery vehicles due to their numerous pharmaceu- tical advantages compared to conventional approaches [7]. The nanoparticles (Nps) surface characteristics, such as the polymer architecture, polymer molecular weight, hydrophilic/hydrophobic character, and surface charge, can significantly impact oral drug delivery [1  ]. Herein, we present a review of recent studies on the development of nanoparticles for oral administration with a specific focus on PLA nanoparticle surface modification using a PEGylation strategy to improve mucus penetra- tion and colloidal stability. Drug delivery systems Drug delivery (DD) is defined as the method or process of administration of pharmaceutical compounds to achieve a therapeutic effect in humans or animals [8]. Many con- ventional drugs cause side effects after administration due to their low solubility, tissue damage by accidental extravasation, premature degradation and poor selectivity for target tissues. The problems associated with conven- tional drugs have been potentially overcome using DD systems [9,10  ,11]. Among the different types of drug-carrying DD systems, nanoparticles (Nps) have been the most used type due to their small particle size and large and modifiable surface [12,13  ]. In addition, Nps have unique advantages com- pared to other drug carriers (i.e. liposomes, lipid-based systems or most micelles) because Nps are more stable in the GI tract [14,15  ]. Three major categories of Nps (i.e. inorganic, polymeric, and biomolecular) have been pre- pared for use as DD systems. However, polymeric Nps, which are defined as particulate dispersions or solid particles with a size in the range of 10–1000 nm [16  ,17], are of much interest for drug carriers due to their biocompatibility, predictable degradation, and di- verse chemistry [18]. The polymeric Nps composition (i.e. hydrophobicity, surface charge, and biodegradation profile) and drug properties (i.e. molecular weight, charge, and localization in the Nps) have a great influence on drug absorption, Available online at www.sciencedirect.com ScienceDirect Current Opinion in Chemical Engineering 2016, 11:14–19 www.sciencedirect.com